The main objective of this research is to study further the biochemical interactions occurring between specific macromolecules which comprise extracellular matrices. These macromolecules include proteoglycans, gycosaminoglycans, collagens and glycoproteins, including fibronectin (also known as LETS: large, external, transformation sensitive glycoprotein). An additional aspect of this study includes an examination of the effects of these macromolecules on cell behavior, especially during morphogenesis and tissue remodelling. During the coming year we will extend our studies with respect to the interactions occurring 1. between basement membrane-type collagens and proteoglycans, 2. between collagen proteoglycan interactions in the developing limb bud, and 3. possible role of fibronectin in regulating collagen-proteoglycan interactions and its effect on matrix deposition. We will continue our studies on the effects of defined substrates on cell behavior, using chondrogenesis as a model system. The latter studies will be extended to monitor biochemically the synthesis of collagen and proteoglycan species in micromass cultures, established from young chick embryo limb buds and grown on known substrates. We will also examine further the relationships of fibronectin to chondrogenesis and matrix deposition in this system. These studies have direct bearing on heritable and congenital disorders of connective tissue and disorders resulting from the synthesis of abnormal extracellular matrix material during tissue remodeling.